A Radical Approach to Making Unnatural Amino Acids: Conversion of C−S Bonds in Cysteine Derivatives into C−C Bonds

• Published in: Angewandte Chemie International Edition 2021-01, Vol.60 (4), p.2155-2159
• Main Authors: Wang, Yingwei, Deng, Li‐Fan, Zhang, Xia, Mou, Ze‐Dong, Niu, Dawen
• Format: Article
• Language: English
• Subjects: Air temperature; Amino acids; Cysteine; Derivatives; Peptides; photocatalysis; radical reactions; Radicals; Room temperature; unnatural amino acids
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202012503

Here we report a general approach to make unnatural amino acids from readily available cysteine derivatives. This method capitalizes on an intramolecular radical substitution process that generates alkyl radicals through C−S cleavage. The resulting alkyl radicals partook in diverse C−C bond forming events. These reactions proceed under mild, photocatalytic conditions at room temperature, and can be performed open to air. The utility of these transformations is further demonstrated in the straightforward synthesis of various unnatural amino acids and peptides that are difficult to access previously. A general approach to convert the C−S bonds in cysteine derivatives into C−C bonds is reported. This method, which capitalizes on an intramolecular radical substitution reaction on sulfur, demonstrates significant scope and yields various unnatural amino acids.